Transcript

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Day 4 Last part
Audio file #8 Renal 2
Penis
Embryo: what is the embryology of hypospadias?
Opening on the undersurface (you pee and it goes
on your shoes) – failure of closure of urethral fold
Epispadias? Opening on upper surface (pee and
goes in face); defect in genital tubercle
Peyronie’s dz: like Dupuytren’s contracture
Priapism – permanent erection, seen commonly in
SCDz bc of the RBC’s and sickle cells trapped in
the vascular channels.
MC cancer of the penis = squamous bc lack of
circumcision. It is more commonly seen in an
uncircumscribed pt – they usually do not clean
(poor hygiene) predisposes – the smegma is
carcinogenic.
Testicle
Cryptorchid testis – testicle doesn’t want to come
down. There are two phases in the decent of a
testicle: transabdominal migration down to inguinal
canal. MIF is responsible for this. The second part
of the trip is androgen dependent. This includes
testosterone and dihydrotestosterone. So, the first
phase is from MIF and the second phase is
androgen dependent. Need testicle down by two
years of age bc if not, has a risk of seminomas.
Still at risk if you get it down. Lets say you went in,
and it look atrophic and other testicle looks normal,
have to take normal one out, too bc it is also at risk.
So, must have testes examines to make sure you
don’t have a seminoma.
Analogy: in turners, they are infertile and have
menopause before menarche, bc by two years of
ages, they have no follicles in their ovaries, and
this is called a streak gonad. This is an ovary
without any follicles. This is analagous to
cryptorchid testes: just like the cryptorchid testes
predisposes to seminomas (which is a germ cell
tumor), so does the streak gonad predispose to a

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germ cell tumor – however, do not call them
seminomas in women, but dysgerminomas. So,
in pts dx’d with Turner’s syndrome, they surgically
remove both ovaries bc of the great risk. They
don’t keep them in there bc lead to cancer.
Orchitis – mumps
Epididymitis – less than 35 = N
gonorrhea/chlamydia, greater than 35 =
pseudomonas
Varicocele – on left side bc spermatic vein
connected to left renal vein, wheras the spermatic
vein on the right is connected to the IVC; bc of this,
the pressures increase, and a varicocele on the
left, leads to increased heat and is one of the most
common causes of infertility – ie what would
happen if you blocked the left renal vein? Would
develop a varicocele. So, if you block the left renal
vein, you will increase the pressure in the
spermatic vein and will lead to a varicocele.
Torsion – spermatic cord twisting; when there is a
torsion of the spermatic cord, it shortens it. This
means that the testicle will go up into the inguinal
canal. This is painful. You will lose your
cremasteric reflex (in normal male, if you scatch
the scrotum, it will contract, which is lost in torsion
of the testicle).
Hydrocele – persistence of tunica vaginalis; when
you have big scrotum, you don’t know whether its
big bc there is fluid in it, or its big bc there is a
testicle in it. So, what do you do? Transilluminate.
If it transilluminates, it is hydrocele. If it doesn’t its
cancer. d/d for painless enlargement of testicle :
cancer, cancer, cancer!! (why they don’t even do
bx, just remove)
Seminoma – MC (best prognosis); huge cells with
lymphocyctic infiltrate. They are the counterpart of
a woman’s dysgerminoma. These will melt with
radiation, have little beta hcG; met to paraortic
lymph nodes – why? Bc they came from the
abdomen, and that’s where they will go.

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MC testicular tumor in child? Yolk sac tumor;
tumor marker? Alpha feto protein
What is worst testicular cancer?
choriocarcinoma – not the same prognosis of a
gestationally derived choriocarcinma in a woman –
you’re dead
Example:: 25 yo male with unilateral gynecomastia
and dyspnea. Chest xray reveals multiple nodular
masses in the lung. So, gynecomastia and mets
dz, - what is the primary cancer? testicle –
choriocarcinoma. Source of gynecomastia: BHCG
is like LH, and therefore it stimulates
progesterone in the male, which increases duct
growth and breast tissue and leads to
gynecomastia
Example:: same scenario, but older man – will lead
to malignant lymphoma
So, older pts get malignant lymphoma (not as
primary dz, but from mets); the testes mets a lot ,
esp in leukemia and lymphomas
Summary:
Worst = choriocacinoma
MC = Seminoma
MC in kids = yolk sac tumor
MC in old = mets malignant lymphoma
Prostate
Hyperplasia occurs in the periurethral portion of the
prostate gland. This is why you get dribbling and
urinary retention as the most common symptom.
Prostate cancer is in the periphery of the prostate
gland within the periphery of your finger. So, when
you press on it, you feel hardness.
Example 75 yo man with urinary retention and
bladder is up the umbilicus and has dribbling –
what is the most likely cause? NOT prostate cancer
– why? Bc for prostate cancer to do that, it has to
invade all the way through the prostate gland to the
urethra/bladder neck. This is prostate
HYPERPLASIA bc it is already around the urethra,
and this is the MCC, not cancer. What male

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hormone is totally responsible for prostate?
Dihydrotestosterone – in embryogenesis, this
hormone fuses the labia to form a scotrum,
extends the clitoris to form a penis and makes a
prostate gland. So, prostate HPY and cancer are
NOT testosterone dep cancers, but
dihydrotesterone dep cancers. If you use a 5 alpha
reductase inhibitor, that will increase testosterone.
This drug will decrease
DIHYDROTESTOSTERONE
MC cancer in men = prostate cancer
Produces osteoblastic mets.
Day 5
Audio file #1 Gyn1
Hirsutism and Virilization
Hirsutism = increased hair in normal hair bearing
areas
Virilization = hirstuism, plus male secondary sexual
characteristics (zits, acne, deeper voice),
clitoromegaly (pathognomonic)
Testosterone is predominantly synthesized in the
ovary. Most testosterone in a woman is from the
ovary.
DHEA sulfate is 95% from adrenals, and is an
androgen. Therefore, if a pt has hirstuism, have to
get two tests – get a testosterone level – have to
fractionate it bc sometimes the total can be normal,
but the free test can be increased, and you get a
DHEA sulfate test. So, if testeterone is
predominantly elevated, it is coming from the ovary
and if DHEA is elevated, it is coming from the
adrenals.
If it is adrenal orgin, it consists of hydroxylase def
(adrogenital syndrome), Cushings, etc..
Hirstuism from the ovaries is a common
phenomenon.
So, when you are evaluating hirsutism, look at
DHEA levels (adrenal origin) and testosterone
levels(ovarian origin).

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One of the common causes of ovarian origin are
polycystic ovarian syndrome.
Polycystic ovarian syndrome
MCC hirstuism = polycystic ovarian syndrome
(or idiopathic)
(Also due to stromal hyperplasia – stroma of the
ovary can make testosterone, or tumors others
ovary)
This dz is a hypothalamic-pit abnormality where
FSH is suppressed and LH is increased. If you
know what LH does, it makes the pathophys easy.
In a woman, LH is responsible for synthesis of
theca interna (which is around the developing
follicle). During the proliferative phase of the cycle,
what is predominantly being synthesized is the 17
keto steroids DHEA and androstenedione. The
androstenedione is converted by oxydoreductase
into testosterone. Then, the test goes across the
membrane of the developing follicle into the
granulosa cells, where there is aromatase. FSH is
put in there. Then, the aromatase in the granulosa
cell converts test into estrodiol and this is where
the woman gets her estradiol (from the
aromatization process). LH is responsible for
synthesis of 17 keto steroids and testosterone in
the ovaries. This is why we will see hirstuism in a
woman with polycystic ovarian syndrome (bc
increase of 17 ketosteroids, DHEA,
androstendione, and testosterone). Obesity is a
common correlation with this dz. This makes sense
bc excess adipose = more aromatase, so the sex
hormones test and androstenedione can be
converted to estrogens in these pts.
Androstenedione is aromatized into estrone (a
weak estrogen). Testosterone is aromatized into
estradiol, which is a strong estrogen. So, we have
a paradox – have a woman with signs of excess
androgens (hirsutism, acne – not signs of
virulization). At the same time, these are being
converted to estrogens so will have endometrial
hyperplasia and therefore have a risk of
endometrial caricinoma. So, there is a combo of
increased androgens and increased estrogens. It
is the increased estrogens that causes suppression

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of FSH via negative feedback, while there is a
POSITIVE feedback on LH. So, bc increased
estrogens, pt is constantly suppressing FSH and
constantly increasing LH, so the cycle repeats
itself. So, you can break the cycle with an OCP bc
the progestin in it will block LH. So, why do they
have cysts? Functions of FSH is to prepare the
follicle. Also, they increase the aromatase activity.
If the FSH is constantly suppressed, the follicle
degenerates and leaves behind a cystic spaces
where the follicle used to be. So, pt has POLYcytic
ovarian syndrome related to chronic FSH
suppression. Can feel these by pelvic exam and
seen with ultrasound.
Menstrual dysfunction
Dysmenorrhea = painful menses (primary and
secondary – MCC primary is too much PGF – a PG
that increases contraction of the uterine
musculature. The MC secondary cause is
endometriosis).
There are also problems with dysfunctional uterine
bleeding – this is NOT a bleeding abnormality
related to a bleeding/organic cause. So, in other
words, it is not bleeding from an endometrial polyp,
its not bleeding from a cancer; this type of bleeding
is a hormone imbalance that causes abnormality in
bleeding.
MCC abnormal bleeding in young lady from
menarche to 20 yrs of age = anovulatory bleeding.
So, if a young lady is bleeding, that is the usual
cause.
What is occurring? There is a persistent estrogen
stimulation that is occurring on the mucosa, and
not enough progesterone stimulation. So, they
develop a lil hyperplasia, there is a build up of
mucosa as the month progresses, and then
eventually the stroma sloughs off and leads to
significant bleeding. So, its mainly an estrogen
primed uterus, without the effect of progesterone
and they do not ovulate related to this. This is the
MCC.

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Amenorrhoea
Primary amenorrhea and secondary amenorrhea
When you think amenorrhea, it can be a prob with
the hypothalamus/pituitary. In other words, is the
hypothalamus putting out GnRH or not? Is the pit
putting out FSH/LH or not? So, is it a hypothalamic-
pit abnormality? Is it an ovarian prob? Maybe the
ovary is not making enough estrogen. Is its an end
organ prob?
This is anatomically related – maybe she doesn’t
have a vagina - Rokitansky-Kuster-Hauser
syndrome, or maybe she has an imperforate
hymen – she’s been having periods all along, and
has blood built up behind it, or cervical stenosis
(DES exposure) – these are all anatomical reasons
for the amenorrhea.
Asherman’s syndrome – secondary amenorrhea,
woman has repeated dilatation and curotoshes(?),
where the stratum basalis is scraped away; have to
leave something behind from which you can
proliferate endometrial mucosa – if you scrape all
the way down the the muscle, will not be able to
menstruate again, and will scar everything off,
leading to an infertile woman.
So, amenorrhea is primary or secondary :
hypothalamic-pit problem, ovarian prob, or end
organ prob. FSH and LH levels help in
distinguishing those 3.
If pt has hypothalamic-pit prob, what would FSH
and LH be? Low.
If had a primary ovarian problem, what would they
be? High.
If you have an end organ defect, what would FSH
and LH levels be? Normal.
What is the first step in the workup of any case of
amenorrhea? Pregnancy test.
Turner’s syndrome:
Primary cause of amenorrhea, webbed neck,
females
Majority are XO, therefore do not have a barr body.
Defects in lymphatics. Can make dx at birth via PE

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– see swelling of hand and feet (lymphedema) =
turners
Webbed neck is due to lymphatic abnormalities –
get cystic hygromas, which are dilated lymphatics
in the neck area and fill with lymphatic fluid and
stretch the skin – bc they stretch the skin, looks like
webbing. Have preductal coarctations. Do not
have MR. some cases are mosaics – XOXX and
there is a remote possibility that they may be fertile.
There are also XOXY’s that are mosaic’s. have
menopause b4 menarche. All of there follicles are
gone by the age of 2, and this is the streak ovaries
(gonad). Therefore, they are susceptible to
dysgerminomas (seminomas are in males are
analogous).
Uterine Disorders
Adenomyosis – glands and stroma within the
myometrium –very common cause of
dysmenorrheal, dyspyrunia, menorragiah,
hysterectomy; does NOT predispose to cancer.
Endometriosis – functioning glands and stroma
outside the uterus (myometrium is INSIDE); MC
location = ovary, causes bleeding in the ovary –
see chocolate cyst (endometroma’s - not cancer,
just endometriosis of the ovary), tube, in pouch of
Douglas
Example: good question to ask if pt has
endometriosis: “Does it hurt when you defecate ?
Yes. How about when your period goes away?”
No, it goes away – this is endometriosis bc there is
bleeding in the rectal pouch of the pouch of
Douglas (there is endometreosis there). The
rectum is filled with stools, and streches the pouch
of Douglas, leading to pain. So, pain on defecation
during the period leads to endometriosis.
Endometrial Hyperplasia
From unopposed estrogen. Always dangerous to
have unopposed estrogen, meaning no
progesterone effect, bc then pt runs risk for
endometrial cancer.

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MCC endometrial cancer = endometrial HPY due
to unopposed estrogen
Pouch of Douglas can collect seeding from ovarian
cancer, pus from PID, unclotted blood from
ruptured ectopic pregnancy
(low part of a woman’s pelvis includes: vagina,
cervical os, uterus, bladder)
Endometrial cancer:
Early vs late menarche – early is worse bc longer
time for estrogen to circulate
Early vs Late menopause – late is worse bc more
estrogen exposure
Obese vs not obese – obese bc the estrogen factor
in adipose (more aromatase), therefore, obese
woman are more susceptible to cancers related to
estrogen - breast cancer, endometrial cancer,
ovarian cancer
Type II diabetics are at increased risk bc 80% of
type II pts are obese (so, the obesity is the cause
of increased risk of endometrial cancer).
Cancer and age brackets
45 = cervical
55 = endometrial
65 = ovarian
55 yo, postmenopausal is when you usually see
endometrial carcinoma. Any woman that has been
in menopause for over 1 yr, and then has
rebleeding has endometrial cancer until proven
otherwise.
1st step in management? Endometrial Bx
Leiomyoma – MC b9 tumor in a woman
Leiomyosarcoma – mitosis prob; MC sarcoma of
the uterus; big bulky tumors (as are all sarcomas);
leiomyoma is NOT a precursor for
leiomyosarcoma.
Example: young woman sudden onset of severe
lower abdominal pain – must do a pregnancy
(look at beta –HCG level) test to rule out ectopic
pregnancy.

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Ovarian masses
Surface derived – derived from the surface of the
ovary
Germ cell types - dysgerminomas (men have
these, too)
Sex chord stromal tumors – make estrogens (ie
granulosa cell tumors - therefore can have
hyperestrinism which leads to bleeding and endo
carcinomas), some make androgens (sertoli leydig
cell tumors of the ovary – assoc with virulization
and hirstuism).
(males just have germ cell tumors)
Follicular cyst
MCC of ovarian mass in a young woman =
follicular cyst
Follicle that ruptured, not neoplastic, accumulates
fluid and leads to peritonitis. It is bad if its on the
right side bc it can be either ruptured follicular cyst,
appedicitus, ectopic pregnancy (ruptured), PID;
look at with ultrasound
Under 35 yo, most ovarian masses are b9
Over 35 yo, most ovarian masses have a greater
potential of being malignant.
Surfaced derived (overall MC)
MC surfaced derived = serous cystadenoma (B9);
serous cystadenocarcinoma (malignant)
(these are the MC overall b9 and malignant
ovarian tumors)
These are also the MC that are bilateral, and the
cystadenocarcinoma has psommoma bodies
(bluish colored – due to apoptosis, destruction of
the tumor cell and replacement with dystrophic
calcification). Also seen in papillary carcinoma of
the thyroid and in meningioma’s
Example:: 65 yo, bilateral ovarian enlargement
(remem they tend to arise at this age)
Any woman that is over 55 and has palpable
ovaries is cancer until proven otherwise bc a
postmenopausal woman should be have ovaries
that are atrophying.

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Example:: 62 yo woman with ovarian mass on the
right – already know its bad bc shouldn’t have a
palpable ovary.
Cystic teratoma
Tooth, sebaceous glands, cartilage, skin, thyroid,,
MC overall germ cell tumor, usually B9
If it is making thyroid, it is called struma ovary
Sex chord stromal tumors
MC = fibromas (B9)
Meigs syndrome: ovarian fibroma, ascites, and
right side pleural effusion – goes away when you
take the ovary out.
Granulosa cell tumor of ovary: low grade malignant
tumor; what does the granulosa cell normally do? It
aromatizes androgens and estrogens, so a
granulosa cell tumor is more than likely an
estrogen producing tumor.
Signet ring cells – is this a primary cancer, or mets
from another site? Site is from stomach – called a
krukenburg tumor; there is NO primary ovarian
cancer that has signet ring cells.
Gestational Disorders
Placenta
Chorionic villus – outside layer =
syncytiotrophoblast, clear cells under the outside
layer = cytotrophoblast; which is making
hormones? Syncytiotrophoblast.
What hormones is it making? B-hcG and Human
Placental Lactogen (HPL) – growth hormone of
pregnancy. Has myxomatous stroma. Vessels
coalesce into umbilical vein, which has the highest
o2 content.
Neoplasms of chorionic villus:
Hydatidiform mole – can be complete (46, XX,
both X c’somes come from father – called
androgenesis) or partial (triploid, 69 c’somes, can
have a fetus present)
The complete moles have a greater propensity to
moving on to choriocarcinoma.

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Causes of choriocarcinoma:
15% of choriocaricnomas are from preexisting
hyadiform mole
25% from spontaneous abortion
25% from normal pregnancy
Hyatidiform moles are b9 tumors of the chorionic
villus; choriocarcinomas are a malignancy of the
trophoblastic tissue (do not see chorionic villi).
Loves to go to the lungs and responds well to
chemotherapy (can even go away in the presence
of mets)
Breast
Picture a schematic with nipple, lactiferous duct,
major ducts, terminal lobules (where milk is made),
and the stroma
Nipple = Pagets dz of the breast
Lactiferous duct = Intraductal papilloma (MCC of
bloody nipple discharge of woman under 50) – b9
papillary tumor, if you press on it, blood will come
out of the areola
Major ducts = where most of the cancers arise from
– invasive ductal cancers, medullary carcinomas,
mucinous carcinomas
Terminal lobules (where milk is made) – MC tumor
= lobular carnicoma, is famous be BILATERAL (so,
lobular tumors are to the breast as serous tumors
are to the ovary in terms of their bilatterallity);
mammography doesn’t pic up lobular cancers.
MCC of mass in breast of woman under 50 =
fibrocystic change
MCC of mass in breast of woman over 50 =
cancer: infiltrating ductal carcinoma (not
intraductal – this means that we are not picking up
the cancer early enough by mammography and
picking up in the intraductal phase, and our
techniques are insensitive – so we are missing the
ductal stage and we are picking up the cancer
when it has invaded – to pick up early, need to get
at 5mm or less).
So, if they are intraductal, has a good prognosis

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Example: 35 yo woman with movable mass in
breast that gets bigger as the cycle progresses =
fibroadenoma
These are the most commons in terms of age and
location
Slide: fibrocystic change – cysts, lumpy bumpy in
breast, more painful as the cycle progresses bc
they are hormone sensitive
Example:: ductal hyperplasia – cannot see;
precursor lesion for cancer that are estrogen
sensitive epithelial cells in the ducts (just like the
endometrial glands are estrogen sensitive, the
glands lining the ducts are estrogen sensitive).
Sclerosing adenosis – in terminal lobules, b9 part
of fibrocystic change (see cysts)
Fibroadenoma
MC tumor that moves around in the breast in a
woman under 35 = fibroadenoma – is the
neoplastic components the glands or the stroma?
It’s the stroma – as it grows, it compresses the
ductstems, so they have slit like spaces; very
common. Even if you know it’s a fibroadenoma,
still get a bx
Breast Cancer
Slide: How do you know its breast cancer? nipple is
hard as a rock – when breast cancers invade the
stroma, they elicit a fibroblastic and elastics tissue
response, making it hard – this is good bc it makes
it palpable. This is why a woman over 50, that
has a painless palpable mass, its cancer.
If its painful and under 50, its rarely cancer (fat
necrosis, fibrocystic change). So, the magic
word is painless.
Outer quadrants of the breast are the MC sites bc
this is where most of the breast tissue is.
Therefore, this would be the MC site for breast
cancer. The 2nd MC site is around the areola.
Slide: nipple being sucked in, whitish mass, stellate
(classic for invasive cancer); on mammography,

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see density with spicules coming out and has
calcified. This is highly predictive for cancer. What
is the first step in management of a palpable
mass? FNA – bc can make a dx and tell if its solid
or cystic (this is also the first step in management
of cold nodule in thyroid, not ultrasound).
Slide: intraductal cancer – netlike arrangement,
called comedocarcinoma, junk that comes out (like
caseous necrosis); has erb-2 oncogene
(aggressive cancers).
Slide: invasive cancer, see tumor cells invading
stroma; see Indian filing – sign of invasive lobular
cancer; seen more often in infiltrating ductal
carcinoma
Slide: eczematous dz around the nipple = pagets
dz of the breast – rash around nipple – cancer of
the duct that has spread to the skin
Slide: inflammatory carcinoma – worst, red,
dimpled skin bc the lymphatics are plugged with
cancer underneath and the lymphatic fluid leaked
out, but the ligaments are still attached, but
increasing the fluid in the interstium, and as it
expands out, it dimples – p’doeu orange – so,
inflammatory carcinoma looks like that bc its
lymphatic filled with tumor, and is the worst of the
worst.
Slide: lobular carcinoma – MC cancer of the
terminal cancer (at the end of the ducts); it is
famous for bilaterality
Slide: lymphedema is a woman that is postradical
masectectomy; when you are doing a modified
radical mastectomy, what are you removing? The
entire breast including a nipple, leaving behind pec
major, axillary resection, and taking pec minor. MC
complication = winged scapula (bc cut the long
thoracic nerve)
The lumpectomy removes the underlying tumor
with a good border of normal tissue around it, take
a few nodes from the axilla (bc have to use for

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staging bc they go to lower axillary first), and then
you do radiation of the breast (good for breast
conservation – same prognosis as mastectomy)
Example:: ERA-PRA = estrogen
receptor/progesterone receptor assay – what does
it mean? Relationship betwn estrogen and its
receptor synthesis. So, if you are in a reproductive
period of your life when estrogen is abundant, the
receptors will be downregulated. This is why in
women that are young, in the reproductive period
of their life, have breast cancer and are ERPRA
negative bc this is what we would expect bc
estrogen would down regulate receptor synthesis.
Whereas, if you are postmenopausal, it leads to up
regulation of the receptors and those women are
ERPRA positive. But what does this mean? It
means that the tumor is responding to estrogen
and need to take away that estrogen affect bc it is
feeding the tumor. How can you take it away?
Tamoxifen – this is weak estrogen, so it hooks into
the receptor of breast tumors, so if there is any left
behind, normal estrogen in a woman can’t get into
it and won’t be able to feed the tumor. So, it’s a
blocker of the receptor.
Complications? Menopausal type symptoms; also,
it is an estrogen so you have the risk of
endometrial cancer. A benefit in the
postmenopausal state with an ERA PRA pos
woman is that it does prevent osteoporosis. So,
cannot give estrogen to a woman that is ERA PRA
pos, but is a candidate for tamox and will prolong
recurrence.
Audio file Day5 #2 Gyn2 (wrong title)it is Endoc
Ch 22: Endocrine Disorders
Primary vs Secondary vs Tertiary
Hashimotos = destruction of the thyroid gland =
PRIMARY hypothyroidism (the gland screws up the
hormone)
Hypopituitarism and hypothyroidism =
SECONDARY hypothyroidism (no TSH to
stimulate)

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Hypothalamic Dz = Sarcoidosis destroying TRH:
TERTIARY (no TRH)
Example: adenoma on parathyroid producing PTH
leading to hypercalcemia = primary
hyperparathyroidism
Example: have hypocalcemia/vit D def, and asked
the parathyroid to undergo hyperplasia, that is
called SECONDARY hyperparathyroidism
Example: what if after a long time PTH keeps being
made = tertiary hyperparathryroidism (rare)
Overactivity vs underactivity of glands
Stimulation test: if pt has underactive gland,
would use stimulation test to see if the gland is
working.
Supression test: if pt has overactive gland, would
use suppression test to see if gland will stop
working.
Most of the time, things that cause overactivity, we
CANNOT suppress them.
There are 2 exceptions where we suppress them,
and they deal with overactivity in the pituitary gland
– 1)prolactinoma can be suppressed bc it can
prevent the tumor from making prolactin;
bromocriptine suppresses it (dopamine analog –
normally, women do not have galactorrhea bc they
are releasing dopamine, which is inhibiting
prolactin (therefore dopamine is an inhibitory
substance – bromocriptine is also used for treating
parkinson’s bc bromocriptine is a dopamine analog
(which is what is missing in parkinsons dz)
2) Pituitary Cushings: b9 tumor in the pitiuitary
that is making ACTH – you CAN suppress it with a
high dose of dexamethasone. These are the only
two exceptions for a tumor making too much stuff.
(There is no way to suppress a parathyroid
adenoma making PTH, or an adrenal ademona

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making cortisol, or a an adrenal tumor from
synthesizing aldosterone – these are
AUTONOMOUS)
Example: pt with hypocortisolism – lets do an
ACTH stimulation test – will hang up an IV drip and
put in some ACTH; collecting urine for 17
hydroxycorticoids (metabolic end product of
cortisol) and nothing happens – so what is the
hypocortisol due to? Addison dz – gland was
destroyed – therefore, even if you keep stimulating
it, you will not be making cortisol.
Example: Let’s say after a few days you see in an
increase in 17 hydroxycorticoids, then what is the
cause of hypocortisolism? Hypopituitarism – in
other words, it’s atrophic bc its not being stimulated
by ACTH, but when you gave it ACTH over a
period of time, it was able to regain its function.
So, with that single test, you are able to find cause
of hypocortisalism.
Can also look at hormonal levels – ie Addison’s
causing hypocortisalism, what would ACTH be?
High; if you have hypopituitarism causing
hypocortisalism, what would ACTH be? Low
Hypopituitarism
MCC in adults = nonfunctioning pituitary
adenoma (within sella turcica – in the sphenoid
bone, hence surgery is transphenoidal surgery,
where the expanded sella turcica is).
Pit Adenoma – usually nonfunctioning and destroys
the normal pituitary over time as it grows, leading
to hypopituitarism.
Sheehans (postpartum necrosis)
Example:: have a pregnant woman, has abruptio
placenta and goes in to hypovolemic shock, but get
out; doing fine and breast feading baby at home,
but suddently stops breast milk production – dx?
Postpartum necrosis – therefore she has infarcted
her pituitary (coagulation necrosis), and this is
residual pitiuatary

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(This is not liquefactive necrosis bc the
pituitary is not part of the brain).
Mech is ischemia and coagulation necrosis.
Pregnant woman have a pituitary gland two times
the normal size. Prolactin is being synthesized –
but a pregnant woman does not have galatorrhea
bc the estrogen and progesterone inhibit release.
So, the moment you give birth, the inhibitory effect
is released and start having galactorrhea. This is
the 2nd MCC hypopit in adult.
MC in kids = craniopharnygioma
Rathke’s pouch origin – this is part of the
embryological development of the pituitary gland –
pieces of it remain and can become neoplastically
transformed into a craniopharygioma. Its not a
malignant tumor, but a b9 tumor in a bad place. It
is MC supra-sellar – (above the sella) – and it goes
down and destroys the pituitary, but likes to go
forward and bumps into optic chiasm, leading to
bitemporal hemianopsia, leading to visual field
defect.
Example:: child with headaches and visual field
defect – do a schematic of it and will ask what the
cause is – craniopharyngioma – tumor of rathke’s
pouch origin.
Growth Hormone
When you have a tumor that is expanding in the
sella turcica, different releasing factors (hormones)
decrease in a certain succession. The first thing
that is destroyed is gonadotropin. So, in a woman,
what would happen? She would have amenorrhea
(secondary amenorrhea). What if I were a man
(what is the analogous condition)? Impotence;
impotence is to a male as amenorrhea is to a
female. Impotence = failure to sustain an erection
during attempted intercourse. The next thing that
goes is growth hormone (which has 2 functions: 1)
increases aa uptake and 2) involved in
gluconeogenesis (hormone that produces bone
and tissue growth is insulin like growth factor-1,
which is present in the liver – aka somatomedins;
so, GH release will stimulate the liver to release
IGF-1 to cause growth of bones linearly and soft

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tissue); an adult with the loss of growth hormone
will not get smaller, but will have the effects of lack
of growth hormone: will start to lose muscle mass
and will have fasting hypoglycemia bc GH is
normally gluconeogenic. So, its not there and not
contributing is func to glucogngeogenesis, leading
to hypoglycemia. What would you see in a child?
Pituitary Dwarfism. Would see hypoplasia
(incomplete development of something). So, pit
dwarfisim is an incompletely developed child, but
everything looks normal. What is the best
stimulation test to see if you are GH or IGF-1
defecient? Sleep. You grow when you sleep –
exactly at 5 am (that’s when GH comes out). So,
the best test is sleeping, then checking blood at 5
am (if it isn’t your def).Why is histidine and arginine
deficient? They are essential to normal growth of a
child bc they stimulate growth hormone. These are
basic aa’s. This is why wt lifters buy arg/his
supplements. So, best test is sleep, followed by
measuring arg and his levels. The third hormone
to go is TSH, which leads to hypothyroidism
(therefore low TSH and low T4 – cold intolerance,
brittle hair, fatigue, delayed reflexes). The next
thing that goes is ACTH , leading to
hypocortisalism. Will be fatigue will a low cortisol
level. Will also lead to hypoglycemia bc cortisol is
gluconeogenic. That last thing to lose is prolactin.
Diabetes Insipidus
Central (lacking ADH) vs Nephrogenic (kidney
doesn’t respond to ADH)
Central: one of the common causes is car accident,
leading to head trauma. The head is shifted and
stalk is severed. One of the first things that goes is
ADH bc it is made in the supraopitic paraventricular
nucleus of the hypothalamus. In the same nerve it
is made in, it goes down the stalk and is stored in
the POSTERIOR pituitary. So, if you sever that
stalk, you sever the connection and leads to ADH
def. Also def in all the releasing factors that are
made in the hypothalamus that stimulate the
pituitary, leading to hypopituitarism (eventually –
but initially will have s/s of DI = polyurea and thrist).

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Nephrogenic: have ADH, but doesn’t work on the
collecting tubule to make it permeable to free
water. Other polyurea’s (DM – mech = osmotic
diuresis, polydipisia – mech = drink too much water
(psychological problem), hypercalcemia leads to
polyurea).
Constantly diluting, but will never be able to
concentrate urine; SIADH is the exact opposite,
where ADH is always there, and will constantly
concentrating, and will not be able to dilute. In DI,
constantly diluting urine, losing free water, and will
never be able to concentrate the urine. So, you are
losing all the water, and serum Na will go up,
correlating with an increased plasma osmolality (bc
most of plasma osmolality is Na).
To test: restrict water – in a normal person, if
you restrict water, the plasma osmolality will go up
to 292 (the upper limit of normal for the osmolality),
750 urine osmolality - what does that mean? Pt is
concentrating the urine. So, if you are depriving a
normal pt of water, it should concentrate the urine;
water is being retained get into the ECF to get the
serum Na into normal range.
Example: pt restricted water and have a 319 and
312 plasma osmolality (which is elevated). So,
they have hypernatremia. If you look at urine
osmolality, it is 110 and 98. So you know that have
DI. So, how do you distinguish central from
nephrogenic? Give them ADH (aka vasopressin).
So, you give it to them and see what happens to
urine osmolality.
If it increases greater that 50% from the
baseline: then it’s central.
It its less than 50% it’s nephrogenic. So, gave
ADH to first guy and it urine osmolality change to
550, indicating that he has central DI. For the
second pt, ADH was given, but only a lil increase in
urine osmalality, indicated nephrogenic DI.
Acromegaly
What is cheapest way for screening for
acromegaly? Ask for an old pic of the pt 10 years

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ago. Gigantism in kid bc epiphyses haven’t fused,
therefore an excess in GH and IGF-1 lead to an
increase in linear growth. Bad dz bc can die from
cardiomyopathy. So, they have excess GH and
excess IGF-1. So, what if you’re an adult with
acromegaly? Will not get taller bc the epiphyses
have fused, but bones will grow wider. One of the
bones in the head that does that is the frontal
bones, so they stick out. So, get a gorilla like
increase in the frontal lobe (bc it increases size of
the sinuses), so the hat size will increase. Your
hands get bigger, feet get bigger, and every organ
in the body gets bigger. Also, you produce a
cardiomyopathy, which leads to death.
Galactorrhea/Prolactinoma
Men do not get galactorrhea bc we don’t have
enough terminal lobules to make the milk. So, if a
male has a prolactinoma, do not expect him to
have galactorrhea. This has many causes. When
woman comes in with it, make sure you ask what
drug they are on - bc there are many drugs that
can stimulate prolactin synthesis.
Example:: OCP’s, hydralazine, Ca channel
blockers, psychotropic drugs. Primary
hypothyroidism can also be a cause, therefore get
a TSH level. Why? Bc if you have hashimoto’s, not
only is TSH increased, but you also have increased
TRH. TRH is used as a stimulation test for
prolactin. So, you must rule out hypothyroidism in
a woman with galactorrhea (so in this case, there is
nothing wrong with the pituitary, but the thyroid,
leading to galactorrhea). So, must r/o
hypothyroidism.
If all this is ruled out and pt has high prolactin level,
dx is prolactinoma (any time there is a prolactin
level over 200 it is always a prolactinoma). When
pts have prolactinoma, why do they develop
amenorrhea? Bc prolactin has a negative feedback
on GnRH. So, this is a cheap birth control pill for
the first three months after pregnancy bc mom is
breast feeding, and the high prolactin levels are
feeding back on the pituitary on GnRH.

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Thyroid
Thyroid studies – do NOT have to know resin T3
uptake and T4 indexes; 3 things need to know: T4,
TSH, I 131 uptake
If TSH is normal, the thyroid is normal. If TSH is
decreased, pt has hyperthyroidism or
hypopituitarism. If TSH is increased, have high
primary hypothyroidism.
Thyroid binding globulin is the binding protein for
thyroid hormone
What is the binding protein for—
cortisol? Transcortin;
calcium? Albumin;
Fe? Transferrin;
Cu? Ceruloplasmin; what % of binding sites
occupied? 30%).
3 of 9 binding sites on TBG are occupied by thyroid
hormone.
Free T4 level. When we measure total T4 level,
there is free T4 and bound T4. The free T4 is the
part that is metabolically active and is converted to
T3. This part is doing all the work (that part that is
bound is not).
What happens if you are on an OCP with an
increase of estrogen? TBG and transcortin
increase. So, increased syn TBG, and is
immediately 1/3 occupied (9 sites on TBG, and 1/3
occupied by T4, so that is 3 T4’s). Bc everything is
in equilibrium, the thyroid senses that it lost 3 T4’s
and replaces them immediatetly. So, has the
FREE T4 altered? No. So what is the TSH?
Normal. What is the T4? Increased (but the free
hormone level and TSH not altered). So, an
increase T4 with a normal TSH means the pt is on
estrogens. This is true for any woman on estrogen
or any pregnant women. So, the total T4 is
elevated bc increased TBG (not be increased free
hormone level) and it automatically has 3 sites
occupied by T4). Same is true for cortisol – if pt is

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pregnant or on OCP, cortisol is elevated but do not
have signs of cushings. Why? Bc transcortin is
increased bc estrogen increasing the synthesis of
it, so there is more cortisol bound to it, but the free
cortisol levels are still normal.
Example:: if football player/wt lifter, assume pt is on
anabolics. They work the opposite. Anabolics
break down proteins that you normally would use
for other things to build up and put them into
muscle. The proteins it likes to go after is binding
proteins. So, when they are on anabolics, thyroid
binding globulin is decreased bc the aa’s that you
would have used to make the binding protein are
instead utilized to make muscles stronger. So,
they won’t work if you are not working aa
supplements.
Example: pt on anabolics, so less TBG being
synthesize bc proteins being used elsewhere
(muscles). The same number of site are occupied,
but missing TBG. So, free T4 is the same, but
missing TBG. So, if a person has a low T4 with a
TSH, they are on anabolic steroids. If a woman
has a high T4 and a normal TSH, what is she on?
Estrogen. If a person has high T4 and low TSH,
what do they have? Hyperthyroidism. If pt has low
T4 and increased TSH, what do they have?
Primary hypothyroidism. Do not need resin T3
uptake to make these dx’s.
I 131 uptake is a radioactive test (remember that
thyroid hormone is tyrosine with iodine on it).
(What are other things involved with tyrosine?
Melanin, tyrosine tyrosinase, dopamine – goes into
the golgi apparatus and becomes melanin,
phenylalanine, dopamine, dopa, NE, epi
(catecholamines), if you put iodides on tyrosine you
have thyroid hormone). So, with hyperthyroidism
(ie graves), thyroid gland will be making more
thyroid hormone. Would we need more iodide to
do this? Yes. So, if you gave a pt radioactive
iodide, will there be increased uptake of radioactive
iodide in that overactive gland? Yes. So, will have
increased I131 uptake. What if I were taking
excess thyroid hormone to lose weight – what

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would that do to my TSH level? Suppress it. So,
when that pt is taking too much hormone, the gland
has atrophied. So, if you have a radioactive I 131,
would there be an increased uptake? No bc is has
atrophied. So, radioactive I 131 is the main way to
distinguish whether a person has true evidence of
hyperthyroidism (GLAND is making too much
thyroid hormone) vs someone that is
surreptitiously/purposely/unknowingly taking too
much thyroid hormone and producing
hyperthyroidism. I 131 is the best test to
distinguish these two types of hyperthyroidism. So,
if its increased, pt has graves (gland is using it); if
its decreased, pt is taking thyroid hormone.
Example:: pt from wt loss clinic – they are taking
thyroid hormone, so they will lose wt at the
expense of hyperthyroidism
Slide: midline cyst – dx? Thyroglossal cyst.
Remember that the thyroid gland was originally at
the base of the tongue and migrates down the
midline to the current location.
Slide: cyst in anolateral portion of neck – dx?
Branchiocleft cyst
(know all branchiocleft derivatives – esp the one in
the head area).
Thyroiditis (inflammation of the thyroid)
The only imp one is hashimoto’s
Grave’s Dz – exophalmos Unique to Grave’s Dz
– excess GAG’s deposited in orbital fat, and
pushing the eye out (pathonomognic for graves);
apathetic graves
OLD people with graves dz have heart prob with
atrial fib. They get heart manifestations. So, any
pt with atrial fib, must get a TSH level to rule out
graves.
s/s hyperthyroidism:
heat intoleranc, sinus tachy, atrial fib, brisk
reflexes, diarrhea, systolic HTN, hypercalcemia,
increased bone turnover (all symptoms are
adrenergic – they are all catecholamine things –

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why? T4 increases the synthesis of beta receptors
(catecholamines are cousins of Thyroid hormone
and they work together. All the symptoms are
adrenergic. What is the INITIAL Rx of graves?
Beta blockers (blocking adrenergic response, then
give PTU to stop the gland from making it – can
stop all the symptoms with beta blocker except one
– sweating)
so, thyroid studies on graves pt: T4 is high, TSH is
low, I 131 is HIGH
Audio File Day5 #3 Endoc
In hyperthyroidism, want to always look at the
face and will see periorbital puffiness, which is
seen a lot bc of GAG’s (also in vocal cords, leading
to hoarseness, tibial area leading to nonpitting
edema)
Mitral Valve Prolapse also has an increase in
GAGs bc dermatan sulfate is responsible for
causing excess and redudency of the valve). Also
seen in Hashimotos. Graves is due to IgG Ab
against TSH receptor, causing it to synthesize too
much. What type of HPY rxn is this? Type II (Ab
against the receptor); MG is also type II HPY (have
Ab against receptor which is destroying the
receptor). In hashimoto’s thyroiditis, they also have
an IgG against the receptor, except instead of
activating the gland, it inhibits it. So, in
Hashimoto’s and Graves, these are both
autoimmune dz’s but at opposite ends of the
spectrum. One as stimulatory IgG while the other
has an inhibibitory one. So, an overlying symptom
that they both have is pretibial myxedema and
GAG deposition. Where do you see a decrease in
GAG’s (ie metabolism of GAG’s)? Lysosomal
storage dzs – Hurlers, Hunters – need lysosomal
enzymes for breaking down dermatan sulfate,
etc…
s/s hypothyroidism –
weakness (MC) bc all pts with hypothyroidism have
proximal muscle myopathy, so they cannot get up
out of chairs , serum CK’s are elevated. Also have

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brittle hair, course skin, slow mentation, periorbital
puffiness, delayed reflex, diastolic HTN
Slide: bx of thyroid gland in Hashimotos’s – no
follicle, but do see germinal follicle bc there is
autoimmune destruction of the gland. There are
cytotoxic T cells that destroying it, and are
synthesizing Ab’s (IgG Abs, hence you see the
germinal follicles), and therefore looks like a lymph
node). Will see a low T4, high TSH, low I 131 (not
necessary to do this test).
Example: pt on estrogen – what will happen to T4?
Increase TSH? Normal (no need for I 131 – this is
bad bc babies thyroid would take it up and its
thyroid would take it up and leads to cretinism)
thyroid hormone is responsible for brain growth in
the first year, so it imp to do thyroid hormone
screens to avoid cretinism (will be severly MR bc
brain depends on thyroid hormone for
development).
Example: Grave’s dz – T4 high, TSH, low, I 131
high
Example: pt on anabolic steroids – T4 low, TSH
normal
Example: Hashimotos – T4 low, TSH high, I 131
low
Example: factitious (taking too much thyroid
hormone and have hyperthyroidism) – T4 high,
TSH low, I 131 low (main factor that distinguishes
from graves)
Goiter
Anytime thyroid is big. Lots cysts.
MCC goiter = Iodine def
Most often due to low iodide levels, so they have
hypothyroidism or borderline hypothyroidism, so
the glands are getting rev’d up, T4 goes up and
TSH goes down (so TSH will be stimulating it, then
not, then it is, etc..).
Rx of choice – thyroxine

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Sometimes have a nodule – nodules that develop
in the thyroid gland get hemorrhaged. There is
sudden increase in hemorrhage due to cyst. Dx
with FNA. Then, give thyroid hormone and many
times these things will get smaller.
In this country, we iodinize salt, so don’t see much.
However, some places people have iodine poor
diets – ie Great Lakes in Chicago area, Britain;
when they get graves dz, due to increase in T3 bc
they are iodide def and do not have enough iodine.
Cold nodule vs Hot Nodule
Means if nodule is taking up I 131 or not. If it does
not, there is an area of lucency, and therefore cold.
If it is hot, there will be a black dot. Why? Bc if the
nodule is autonomously making thyroid hormone,
what is the TSH? Decreased. If the TSH is
decreased, would that suppress the normal portion
of the thyroid? Yes, so it undergo atrophy and not
take it up, leading to black dot (wouldn’t see
anything else). What is chance that a cold nodule
is malignant in a woman? 15-20%. Most cold
nodules in an older woman are benign. Most are
cysts. A small % is follicular adenoma. Any cold
nodule in a MAN is cancer until proven otherwise.
Any cold nodule in a child is cancer until proven
otherwise. Any PERSON that has been exposed
to radiation and has a cold nodule has CANCER
(papillary carcinoma of the thyroid – radiation
exposure in head/neck area).
Cancers of the thyroid
Need to bx (cannot tell if malignant just by looking
at it) – this is true for follicular adenoma, something
b9, multinodular goiter. Done with FNA.
1. Papillary cancer would show up with a cold
nodule, and has Psammoma bodies.
Papillary carcinomas mets to cervical lymph
nodes next to them. They commonly do
this, and have a good prognosis. This is the
only assoc with radiation. Annie orphan
nuclei.
2. Follicular cancer – 2nd MC type, invades
vessels. Do not go to lymph nodes. Spread
hematogenously, therefore often go to lungs
and bone.

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3. Medullary carcinoma – some cases are
sporadic and other cases have AD
relationship; assoc with MEN syndromes
(multiple endocrine neoplasia I, IIa, IIb)
Pink stain – stain with congo red and see
polarized apple green birefringence =
amyloid A (which came from calcitonin);
what is the tumor marker? Calcitonin (which
is the screening test of choice)
Example: where would the cancer be located in the
body where the tumor marker is converted into
amyloid? Medullary carcinoma of the thyroid
MEN I – pit tumor, parathyroid adenoma,
pancreatic tumor (usually Zolinger Ellison, leading
to peptic ulcer).
MEN IIa – medullary carcinoma, pituitary ,
pheochromocytoma
MEN IIb – medullary carcinoma,
pheochromocytoma, mucosal neuroma
How do you screen? Ret protooncogene (unique to
coding for receptors in this syndrome).
Prognosis (best to worst):
Papillary>Follicular>Medullary
PARATHYROID GLAND
Pt can have tetany with a normal total Ca. Ca is
bound and free – it’s the free Ca that is
metabolically active (which is true for ANY
hormone – the part that is bound is totally
metabolically inactive). So, who does Ca interact
with? PTH
So, if Ca is low, the PTH is high, and if Ca is high,
PTH is low. Roughly 1/3 of the binding sites in
albumin are occupied by Ca. So, in other words,
roughly 40% of the total Ca is bound to albumin.
47% is ionized Ca floating around and the rest is
phosphate and sulfates. The ionized Ca is the
metabollicaly active form. MCC overall of
hypocalcemia = hypoalbuminemia. Have low
albumin level, therefore decreased level, and less
of albumin binds Ca. So, before you look at PTH

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levels, look at albumin levels – if that is low, this is
the cause of hypocalcemia. This is not affecting
the free hormone level, just that albumin is
decreased. This the same as TBG being
decreased, leading to decreased T4.
Alkalosis (resp or metabolic): have decreased H
ions, and pH is increased. What are the acidic
aa’s? Glutamate, Aspartate. Why are they acidic?
Have COOH groups (as opposed to basic aa’s ,
which have more basic NH groups).
The reason why albumin is such a great binder of
Ca is bc it has the most negative charges in the
body, bc it has the most acidic aa’s in it. So, if you
have an alkalotic state the COOH groups become
COO “-“ groups. Bc if you have less H ions, its
COO”-“. So, albumin has MORE of a negative
charge in an alkalotic state, which means it can
bind more Ca. So, where does it get it from?
Ionized free Ca (so a bunch of ionized free Ca
binds to the the albumin). However, we have NOT
altered the total, just took it. It doesn’t affect the
total, but it DOES decrease the ionized Ca level,
leading to TETANY. So, total is the same, but the
ionized level has decreased. What is the mech of
tetany? Have threshold for the AP before the nerve
is stimulated. Then you have a resting membrane
potential. So, a decreased ionized Ca level will
lower the threshold for activating the nerve and
muscle. If its -60 for normal threshold. Pt is
partially depolarized, therefore doesn’t take a lot to
activate the muscle or the nerve (which is the mech
of tetany) – so you are lowering the threshold. In
hypercalcemia, the opposite occurs and you are
increasing the threshold, so it takes more ionized
Ca to activate the nerve.
PTH on y axis and Ca in x axis – ht of square =
PTH and width = Ca
Low serum Ca, low PTH = primary
hypoparathyroidism
MCC = previous thyroid surgery
Example: pt goes in to remove thyroid cancer
(these days they autotranplant it to the arm)

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Example: newborn with cyanosis, irritable and xray
of chest shows not anteriormediastinum shadow –
dx? DiGeorge – hypoparathyroidism and no
thymus
Example: low Ca, high PTH = secondary
hypoparathyrodism – so whatever is causing the
hypocalcemia is causing a compensatory increase
in PTH (called secondary hypoparathyrodism – the
MCC of this is renal failure bc these pts have
hypovitaminosis D, which decreases Ca and
increases PTH). So, any decrease in Ca with
cause a compensatory increase in PTH.
Example: high Ca, high PTH = primary
hyperparathyroidism = gland is not obeying
negative feedback. This is MCC hypercalcemia is
a community;
If pt is in a hospital, MCC hypercalcemia = mets to
bone (malignancy induced). Most hypercalcemia
pts are asmptomatic; if they ARE symptomatic,
they have stones (Ca stones, which is the MC
symptomatic presentation for hypercalcemia).
Labs: increased Ca, increased PTH, low phosphate
(normally PTH increases Ca reabsorption and
decreased phophorus reabsorption). Almost always
over 50 yo
Example: high Ca, low PTH = all other causes
except primary hyperparathyroidism. MC due to
malignancy. Can PTH like peptide cause
hyperCa? Yes (so if you measure PTH it will be
normal). Squamous cell of the lung, renal
adenocacinoma, or mets to bone (breaking bone
down), sarcoidsis (leading to hypercalcemia),
multiple myeloma (leading to hypercalcemia) all will
have LOW PTH. So, what is the ez’est way to
determine hyperCa in a pt? PTH level
(if its high, its primary hyperparathyroidism; if its
low, its all the causes – ie malignancy).
ADRENAL GLAND
Cushing Syndrome
PURPLE striae, obesity, thin extremities

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MCC = pt on long term steroid therapy (ie pts with
renal transplants, pt on immunosuppressant,
Lupus)
If this is excluded, need to think of 3 sources:
pituitary Cushings, adrenal Cushings, ectopic
Cushings. Which of the three will have the highest
ACTH levels? Ectopic (small cell carcinoma).
Which would have the lowest ACTH levels?
Adrenal. Why? Bc its making cortisol, which would
suppress the ACTH. Pit Cushings is usually a b9
tumor making ACTH.
There are 2 good screening tests for Cushings
(when you have excluded the fact that they are not
on steroids). The screening tests are: 24 hr urine
test for free cortisol. This is looking for cortisol in
the urine, not attached to any protein (so it’s free).
It must mean that you have a lot of excess of it to
have that much of it in your urine. This is the BEST
screening test for Cushings. This test distinguishes
Cushing’s syndrome from Cushingoid obesity.
Example: see obese pt with Cushing’s symptoms
and you think they have Cushings; however, get a
24 hr urine cortisol test and it’s normal. If it’s
increased, they truly have Cushings – in other
words, they have 99% sens and specificity.
They will ask about dexmeth suppression test
(low vs high dose). What is dexamethasone? It’s a
cortisol analog. If you give dexamethasone to a
normal person, it will suppress ACTH. If you
suppress ACTH, the cortisol levels with be low,
indicating the cortisol levels are suppressible. So,
what happens when you give a LOW dose of
dexamethasone in a pt with Cushings – will you
suppress their cortisol? No. So, you see a lack of
suppression. Therefore pt has cushing’s. However
the LOW dose just tells you pt has Cushings, not
what kind they have, so it just a screening test (if
you did a 24 hr cortisol urine level, it would be
positive). Remember that there are two endocrine
dz’s that you CAN suppress – PITUITARY
Cushings and prolactinoma. So, if you give high
dose of dexamethasone, you are able to suppress

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the ACTH release by the pituitary and cortisol goes
down. It will not be suppressed in adrenal and
ectopic Cushings (small cell).
[Read last sentence if you get a long question]
Example: for one of these, they will describe
Cushings, and ask about dexmeth suppression –
first thing to do is look at high dose suppression – if
its suppressed, its automatically pituitary cushings
(not a hard question!)
So, why do the pts look like this? Pt has
hypercortisolism, which is gluconeogenic. So,
need substrates for gluconeogenesis – main
substrate is aa from muscles. Where are the
muscles located? Arms and legs – so pt will get a
break down of muscle in the extremities, which is
why they have thin arms and thin legs. Then will
get alanine transaminated and get pyruvate. So,
will always have thin arms and extremities. Bc it is
gluconeogenic, what will the glucose be? High.
What does that do to insulin release? Increases it.
What does insulin do to fat? Increases fat storage.
What part of the body have the most adipose?
Face and trunk. So, you are getting an increase in
deposition of TG in the face and trunk and back.
So, the thin extremities is due to breaking down
muscle for aa’s in gluconeogenesis. The moon
facies, buffalo hump and truncal obesity is due to
increase in insulin and fat deposition. The stretch
marks are due to obesity, and they are purple bc
cortisol decreases collagen synthesis. Will get
structurally weaker collagen. Its like purpura within
the stretch mark (like senile purpura). Break down
the vessels bc increase in cortisol.
Example: Trousseau’s sign – sign of tetany; this
pt has HTN, hypernatremia, hypokalemia, and
metabolic alkalosis – dx? Primary aldosteronism.
(have tetany bc alkalosis – neg charges on albumin
are increased, and ioninzed Ca level decreases).
Aka Conn’s syndrome
Adrenal Medulla tumors
MC in adults = pheochromocytoma (b9, HTN)
(so, adult, HTN, tumor in adrenal medulla = pheo);

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have unstable HTN – anxiety, sweat a lot; get a 24
hr urine test for VMA and metenephrine (these are
metabolic endproducts of NE an Epi (so, anxious,
sweating, HTN). Are there assoc with
pheochromocytoma? Yes – MEN IIa and MEN IIb,
neurofibromatosis (ie pt with neurofibromatosis with
HTN – what test you get? VMA and metanephrine
24 hr urine, bc high assoc with pheo).
MC in kids = neuroblastoma (MALIGNANT)
Both of these are from renal medulla, both are
neural crest origin, both produce HTN. Pheo =
adults ; neuro - kids
Waterhouse Friderichsen Syndrome
N. menigitidis
Example:: 12 yo, gram “-“ diploccocus, high fever,
nuchal rigidity, spinal tap found neutrophils and
gram “-“, kid then ‘crashed’ – started to get
petechial lesions all over the body, hypovolemic
shock, died, on autopsy both adrenal glands are
hemorrhaged – Dx? Waterhouse Freidrickson
MCC meningitis from 1 month to 18 yrs of age =
N meningitidis. It is the ONLY meningitis with
petechial lesions (and they always mention this).
So, if they give meningitis and petechia, know is N
meningitis. If they are hypovolemic, they
hemorrhaged their adrenals and went into
hypvolemic shock, also, they have no cortisol or
mineralocorticoids.
Cause of hypocortisolism that is chronic =
Addison’s dz
MCC Addisons = autoimmune destruction of the
gland (used to be TB due to autoimmune
destruction). The entire adrenal cortex is
destroyed, therefore the mineralocorticoids and
glucocorticoids are low. So, there is low cortisol
with HIGH ACTH. What does that do to
melanocytes? Increases them, leading to
hypigmentation in the mouth and elsewhere. There
is NO aldosterone. There are 2 pumps (Na/K
pump and proton/K pump). Are you gonna lose
Na? Yes – which will lead to hyponatremia and
HYPERkalemia (peaked T waves). Will you be
able to get rid of the protons in the urine? No –

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therefore will have metabolic acidosis. So, you
have hyponatremia, hyperkalemia, metabolic
acidosis, hyperpigmentation.
Example: ambiguous genetalia – what is first step
in management? C’some analysis – have to find
out what the genetic sex is. It’s XX. So, pt has
ambiguous genetalia, female, phenotypically
cannot tell, so it’s female pseudohermaphrotide
– (play odds) – adrenogenital syndrome due to 21
hydroxylase def.
17 hydroxylase is responsible for 17 ketosteriods
(include DHEA, androstenedione, and are weak
androgens). Androstenedione can be converted
into testosterone and testosterone into
dihydrotestosterone.
17 hydroxycorticoids are 11 deoxycortisol and
cortisol
So, if you have an increase in 17
hydroxycorticoids, this is an increase in 11
deoxycortisol and cortisol
If you have an increase in 17 ketosteroids, (17,
KS) it’s an increase in DHEA and
androstenedione.
When you have an enzyme def, things prox to
the block increase and things distal to the
block decrease
With 21 hydroxylase def, decrease
mineralcorticoids and glucocortiocoids and
increase androgens, lead to ambiguous genetalia
(excess androgens), lose salt, high ACTH,
therefore hyperpigmented
With 11 hydroxylase def – decreased cortisol,
decreased aldost, but increased 11
deoxycorticosterone (weak mineralcoricoid),
increased 17 hydroxy’s and 17 ketos – lil girl will
have ambiguous genitalia, lil boy will have
precocious puberty (excess androgens), HTN
17 hydroxylase def – no androgens, increased in
mineralocorticoids (HTN), so if it’s a lil boy he won’t
have test and will look like a female bc no
development (no external genitalia bc no 17 keto’s,

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test, or dihydrotest). In a lil girl – she will be
underdevoped.
Islet cell tumors
Only 2 to know: Insulinomas and ZE syndrome
ZE: making too much gastrin, leads to peptic ulcers
Insulinoma: is pt injecting or do they really have
insulinoma?
When you break proinsulin down into insulin, you
release C peptide, so for every insulin molecule
that is released, there is C peptide that is released
with it. So, if you inject human insulin into yourself,
and produce a low glucose level and C peptide will
be SUPPRESSED.
If you have a islet cell tumor, glucose will be low,
insulin will be high and C peptide will be
INCREASED.
Example: pts that have access to insulin get this
(Drs, nurses, pharmacists)
Audio file Day5 #4 Musculoskeletal
Diabetes Mellitus
Type 1
Absolute insulin deficiency
Antibodies against islet cells
DKA
HLA relationship
Insulin used (always)
Type 2
Family history of diabetes
Obesity
Amyloid in islet cells
Hyperosmolar non-ketotic coma
Insulin used when eventually pt get resistant to
SFU
PATHOGENESIS: 2 mechanisms:
1) Osmotic Damage
Tissue has to have aldose reductase: only 2 have
them:

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i) Lens, glucose sorbitol, osmotic reactive,
absorbs water into the lens
Retinal vessels in lens get weak, then destroyed
due to microabsesses and can rupture and lead to
blindness.
ii) Scwann Cells: MCC cause of peripheral
neuropathy is Diabetes: MECH: osmotic damage
2) Non-enzymatic Glycosylation
Renders the BM permeable to proteins: Hyaline
arteriolosclorosis, diabetic nephrophathy
HbA1c: long term control of DM.
Slide: Retina in a diabetic-microaneurysms (red
dots)
Slide: Retina in a diabetic-neovascularization
Example: 50 yr old, blurry vision; gets a
prescription from a optometrist, new glasses, one
month later, blurry vision again. Gets new prescr,
one mth later, blurry vision again. Dx: Diabetes.
Glucose is being converted to sorbitol-water is
going in and changing the refractive index. Classic
question. HAVE to get a FASTING BLOOD
GLUCOSE.
Lab: Fasting glucose >126 mg/dl on two separate
occasions.
Example: Beh Sc link: The FBS level has been
decreased from 140 mg/dl to 126 mg/dl. Is this
increasing the specificity or the sensitivity of the
test?
A: HIGH Sensitivity. By bringing it lower ie closer to
the normal range, you are going to be able to pick
up more people with diabetes. When it was 140, it
was high sp: to eliminate false positives. So it was
unequivocally a diabetic if it was > 140.
Glucose tolerance test, don’t worry about it.

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Gestational Diabetes
Def: Woman who did not have diabetes, but after
becoming pregnant develops diabetes.
Risk factors for baby:
RDS, premature delivery
Women with GD, are at a higher risk for developing
diabetes later on.
Amyloid in Beta islets: Type 2
Antibodies against islets; inflammation: Type1
(Coxackie virus implicated)
HLA correlation: HLA DR3 and DR4=Type 1;
propensity for developing Type 1, if certain
environmental factor comes in such as infection:
Coxsackie, mumps, EBV
HLAB27: Ankylosing Spondylitis
Env factors:
Chlamydeal Infection
Ulcerative Colitis,
Shigellosis
Psoriasis
Musculoskeletal System
Need to identify crystals in synovial fluid
Gout
Pseudogout
Rhomboid crystals in synovial fluid==pseudogout
But Pseudogout could also have needle-shaped
crystals (like those of mono-sodium urate in Gout)
which makes DD difficult. So you use a special
filter to make the whole slide red and then the
crystals are made to look yellow or blue.
When the color of the crystals is yellow when the
plane of filter is parallel to the analyzer=
Negatively birefringent =GOUT

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East west direction: color is blue and parallel to
analyzer=Positively birefringent =
PSEUDOGOUT (calcium pyrophosphate)
Arthritis
Osteoarthritis
Progressive wearing down of articular cartilage
Sometimes leads to reaction to injury: SPUR
formation—at the margin of the joint= Heberden’s
node: osteophyte in the joint
Note the enlargement of the DIP (Heberden's
nodes) and PIP joints (Bouchard's nodes),
enlargements represent osteophytes.
Rheumatoid Arthritis
Inflammatory joint dz; enlarged MCP joints
Rh factor sets up the inflammation: IgM Ab against
IgG. IgG is in synovial fluid. IgM-IgG form
complexes, activate the complement system,
damage the joint, synovial fluid gets inflamed,
starts growing and growing, starts growing over the
articular cartilage= PANNUS; hyperplastic synovial
fluid. (different from Tophus)
Joints can get fixed, and ankylosed and cannot
move.
Don’t get fixing of the joint in OA.
If rheumatoids don’t keep moving their joints, and if
it is not controlled using anti-inflammatory drugs
then eventually they cannot move it at all.
Slide: Rheumatoid nodules. Can be seen in
Rheumatic fever as well.
Example: older pt having trouble eating and
swallowing crackers, feels like there is sand in my
eye all the time. On examination: eyes and mouth
are dry. Dx? Sjogran’s Syndrome. Pt with RA and
auto-immune destruction of lacrimal glands,
salivary glands. Keratoconjunctivitis sicca

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Rheumatoid nodules in lung +
pneumoconiosis==Caplan Syndrome
Treatment of RA= Methotrexate
Example: Pt with RA, develops a macrocytic
anemia with hypersegmented neutrophils, neuro
exam is normal, interstitial fibrosis in lung. What is
the drug? Methotrexate
Gout = podagra
Big toe, usually first one to be involved; usually at
night.
Monosodium urate crystals are precipitated and
taken up by the neutrophils that phagocytose it and
release chemicals—inflammatory reaction.
Don’t define Gout based on Uric acid level.
Elevated uric acid does not necessarily lead to
gout. About 25% of people might have elevated
uric acid.
Dx: HAS to be by presence of uric acid crystals in
the joint.
Treatment: Indomethacin to control inflammation.
Cause: over production (Rx=allopurinol: blocks
Xanthine oxidase) or under excretion of uric acid
(>90% of cases) Rx=uricosuric drugs like
probenecid and Sulfinpyrazone
Chronic Gout = tophus: deposition of
monosodium urate in soft tissue—malleolus
Very disabling as it erodes the joint.
Rx= allopurinol
Slide: Tophus that was polarized showing MSU
crystals
Slide: X-ray of digit showing erosion by tophus
Genetics of Gout:
Multifactorial inheritance

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Another Env trigger in HLAB27 positive pt:
Ulcerative Colitis
Septic arthritis due to disseminated
gonococcemia
Note the hot knee and the pustule on the wrist, on
aspirating: gram negative diplococci
STD= Sexually Transmitted Disease
S=Synovitis=joints
T= Tenosynovitis= joints in hands and feet
D= Dermatitis=pustules
MCC of septic arthritis in US= Gonorrhoea
For it to become disseminated, need to be deficient
in the final pathway of Complement system: C5-C9
(some say C6-C9)
Slide: Note the Ixodes tick (vector of Borrelia
burgdorferi and Babesia microti), note the
erythematous rash in the bottom screen - the tick
bite is in the center of the rash and the rash
extends out in concentric circles from that point, the
rash is called erythema chronicum migrans
(pebble thrown in water) Pathognomonic of Lyme's
disease
Early form Rx: tetracycline
Chronic Lyme’s Disease: Apart from disabling
joint disease: myocarditis plus bilateral Bell’s palsy:
CN VII involved + pt will have Babesiosis
Idiopathic: is usually Unilateral Bell’s Palsy=
Herpes Simplex
Above Pt develops Hemolytic anemia, what did he
see in his peripheral blood smear? Babesia microti
(ring form similar to Plasmodium falciparum)
Remember: the Ixodes tick has the reservoir for
Borrelia burgdorferi (white tailed deer that has
Babesia microti) AND Babesia microti intra-
erythrocytic parasite

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Rx: Ceftriaxone
Bone Disorders
Osteogenesis imperfecta
Slide: Kid with an eyeball, blue sclera: AD disorder
with defect in synthesis of type I collagen, note the
blue sclera- loss of collagen in sclera allows bluish
color of choroidal vessels to shine through:
Osteogenesis imperfecta (NOT foreign body!)
“brittle bone disease” cant break bone down
Question: what’s the defect? Defective synthesis of
type 1 collagen
Question: what’s the mechanism of development of
blue sclera?
Collagen in sclera, type 1 is defective, so it is so
thin, so you can see the underlying choroidal veins
that gives the blue color.
Osteopetrosis = “marble bone disease”
Defect in too much bone: defect in osteoclasts
Osteoporosis
Slide: Decreased width of inter vertebral cartilage.
Note the collapse of the vertebra due to loss of
bone mass: patients lose more bone than is
replaced
Slide: Dowager’s Hump
Mech: Postmenopausal osteoporosis is due to the
loss of the inhibitory effect of estrogen on the
release of interleukin 1 from osteoblasts; not
enough estrogen to stop the activity of Interleukin-1
(osteoclast activating factor) from breaking your
bone down.
Osteoporosis: Overall reduction in bone mass.
Both mineral AND organic component. WHOLE
mass of bone is reduced.

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Osteomalacia: Decreased mineralization of bone:
organic part of bone is normal. Cartilage is ok,
osteoid is ok; its not getting mineralized
Dx of osteoporosis: Dual beam Absorptiometry:
density of the bone in whole body is measured.
Non invasive, very easy.
MC fracture: compression fracture: lose stature,
2nd MC fracture: Colle’s fracture of distal radius.
Question: Is swimming a good exercise for
preventing osteoporosis: NO. Because no stress
on bones. It is great exercise for aerobics. But it
does not prevent osteoporosis. Walking is good.
Weight bearing is even better than walking! Walk
with Dumbells! Get aerobics and inc in bone mass!
HAVE to stress bone to build it up.
Example: In space, lack of gravity and astronauts
are given bisphosphonates, Vit D and calcium to
get bone density back: because serious prob of
osteoporosis in space.
Tip: reproductive women need to:
1) Exercise
2) 1500 mg of Ca everyday
3) 400-800 units of Vit D
4) Vit pill that contains Iron
Bone Tumors
Exostosis (osteochondroma)
Note the cartilaginous cap on the surface of the
bone. This causes a protuberance of the bone.
This is the most common benign bone tumor.
Chondrosarcoma of the hip
MC malignant one
Osteogenic sarcoma
Slide: Note metaphyseal origin of the cancer and
extension into the muscle, note the splinter of
periosteum that is elevated which would
correspond to Codman's triangle

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triplet repeats added on, leading to a more
defective protein and the dz gets worse and worse.
Example: genetic counselor telling couple that they
have a dz, where if are to have children, the dz will
be fatal in their children. The couple didn’t listen to
their counseler, had a child and the child died only
after 1 month. What was it and what is this: an ie
triplet repeat disorder (anticipation) Muscle
weakness in face (so mouth is drooped open).
Example: pt with failure to release grip on golf stick
(or when shaking hand) – they cannot relax their
muscle grip, diabetes, cardiac abnormality
Myasthenia Gravis
AutoAb against Ach receptor – it’s an IgG Ab,
therefore is an Example: of type II HPY, like
Grave’s, which is an IgG Ab against the receptor
(by definition, this makes it type II). Whether you
destroy the receptor or just block it is irrelevant.
Ach cannot hook into it and therefore there is
muscle weekness. The first muscles are the lids,
which leads to lid lag. They also get double vision
bc muscles of the eye are messed up, leading to
diplopia. Eventually, they get dysphagia for solids
and liquids (gets stuck in upper esophagus, bc this
is where there is STRIATED muscle). Eventually
muscle dz prevails throughout.
Feel energized in the morning and feel tired at
night. Tensilon test positive. Can die.
Rx is acetylcholinestrase inhibitors. By giving an
inhibitor, block the breakdown of Ach and build up
Ach. With few receptors you have in there, there is
a larger chance of hooking up to the receptors and
pt does well. However, eventually, no receptors
there and it doesn’t matter how much Ach is there,
so pt is screwed. Then, her only option is a
thymectomy.
The thymus is in the anterior mediastimun. Trick
question: they can ask, what is the pathology?
They can describe MG and ask, what do you
expect to see in the mediastinum? Do NOT put
thymoma. This is a malignancy of the thymus and

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does occur in 15-20% of cases, but isn’t the MC
pathology seen in the thymus in a pt with MG. See
germinal follicles in the thymus (remember, this T
cell country, not B cell country, so its abnormal to
have germinal follicles here) – they are the ones
making the Ab causing the MG. So, by doing a
thymectomy for Rx, you are removing the Ab
producing tissue. 1/3 pts get a complete cure. 1/3
get a partial cure, and 1/3 die bc they waited too
long for thymectomy and Rx and didn’t have
receptors, anyway. So, B cell hyperplasia is the
MC thing you see, not thymoma. This where the
Ab is being made.
Lupus
Butterfly distribution on the face (malar rash)
Of all the autoimmune dz’s this one is the most
likely one to have a “+” ANA (99% sensitivity). The
Ab’s you want to order to prove that its lupus are
anti-Smith Ab (which has a 100% spec, therefore
no false pos – therefore 100% PPV) for lupus,
meaning that if you test “+” for this Ab, you have
Lupus. The other Ab is anti –dsDNA – this not only
indicates that you have lupus, but also that you
have KIDNEY dz. That has a 98% spec, too. So,
these are two good Ab’s to confirm lupus. Morning
stiffness is present in lupus (simulates Rh
arthritis/photophobia), rash, pericarditis; LE cell
prep – Anti – DNA Ab’s are phagocytosed by
neutrophils, and they have altered DNA. Not
specific for lupus (waste of time).
Progressive Systemic Sclerosis/CREST
Tight face, telangiectasia, Raynauds, dysphagia
(solids and liquids), dystrophic calcification,
sclerodactly; if kidneys involved, it is progressive
systemic sclerosis, NOT CREST (doesn’t involved
kidneys).
Dermatomyositis
Racoon eyes, elevated serum CK, rash over the
PIP (goutren’ patches), highest assoc with
underlying cancer.
Sjogrens syndrome

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Bc the fungus involves the inner portion of the
shaft, there are no fluorescent metabolites, and is
Wood light negative
All the other superficial dermatophyte infections
including Tinea corporis (ring worm)
Example: red outer edge and clear center, what is
first step in workup? Scrape outside and do KOH
prep, and see hyphae and yeast forms. All other
superficial dermatophyte infections (except
Tinea capitis) are due to trychophyton rubra.
What is the color around Tinea capitis? Red (=
rubra) (how to remember it).
Molluscum contagiosum
Sandy like material in crater, children, self inoculate
Poxvirus makes these (DNA virus)
Volcano crater look, with sandy stuff in it
Pityriasis Rosea
Example: rash on butt – non pruritic rash, NON
INFECTIOUS; oblong looking with red on outside
and pale in middle. You think this is T corporis, but
its oblong (and not circular). Do a KOH prep, find
nothing; then put topical steroids and doesn’t go
away; 3 days later comes back with rash in the line
of langer in Christmas tree like distribution; not an
infectious dz, like a herald rash; not a fungus
Dysplastic Nevus syndrome
Example: precursor lesion for malignant
melanoma; if you have over 100 nevi all over body,
you have dysplastic nevus syndrome
Very common
Must go to dermatologist once a year bc need to
look at dysplastic nevi.
Could be a precursor lesion for malignant
melanoma.
4 diff types of malignant melanoma
What is first step in management? Excision
Example: superficial spreading malignant
melanoma (MC)
Example: on face of older pt – Lentigo maligna
melanoma; irregular border, corn colored, LEAST
likely to met of all malignant melanomas.

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Example: black pop’n do not get malignant
melanomas bc the black pigment in the skin
prevents UV light damage and propensity for
cancer. however, there is one type of cancer they
malignant melanoma they CAN get:
black pt with dyspnea, on xray find multiple mets all
over body. Bx is done and pt has malignant
melanoma, which part of the body would you
examine to find the primary dz? Under the nails,
palms or sole of the feet – this is Acrolentiginous
malignant melanoma (‘acro’ means edge of/tip of)
– this is the MOST AGGRESSIVE of all the
melanomas. This has nothing to do with radiation.
Pagets dz looks similar
Example: Nodular malignant melanoma – also very
aggressive.
The most important thing affecting prognosis is
depth of invasion (key to prognosis – magic # is
.76 mm). If its less than .76, its not gonna met.
Toxins
2 poisonous spiders –
Black widow
Has a neurotoxin – causes spasm of the muscles
in the upper thighs and abdomen so strong its
almost like tetanus; pain muscle contractions, esp
in the abdomen. There is an antivenom, painful
bite
Example: person went down into their cellar, lifted
boxes, felt sharp prick on finger, and developed
contractures over a period of hrs – due to black
widow bite.
Brown recluse spider (aka violin spider)
Painless bite, has a necrotoxin, leading to ulcer
So, neurotoxin for black widow, necrotoxin for
brown reclous
Where is receptors to androgens? Sebaceous
glands (this is why men get more zits than woman
– testosterone will release lipid rich material which
gets into the hair follicle. Then, if you have
proprionum acnei (anaerobe) it has lipases that

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breakdown fat from the sebaceous gland and
produces FA’s that irritate the follicle and end up
with acne. So, men more likely to get it bc they
have acne
It all occurs in the erector pili muscle of the skin.
So, there are androgen receptors sebaceous
glands and erector pili muscle.
Drug used to prevent hirsutism?
Spironolactone (same drug used to block
aldosterone); this drug is good bc it blocks
androgen receptors and therefore prevents
hirsutism. Can also lead to gynecomastia.
CNS
Spinal fluid – derives from choroid plexus in the
ventricles. In the lateral, 3rd and 4th ventricles. Its
an ultrafiltrate of plasma. What is the difference in
serum and spinal fluid? Way more protein in spinal
fluid bc it’s an ultrafiltrate. Cell? Hardly any cells in
spinal fluid (none). Glucose? Lower in spinal fluid –
about 60% of what it is in serum (if the spinal fluid
glucose level were low, then something is in there
utilizing it for energy such as bacteria or fungus or
cancer cells). Is there anything MORE in spinal
fluid than serum? Chloride (way higher in spinal
fluid than serum) - around 120. These are imp bc
there are injuries to the head.
Example: baseball that hits the eye in an orbital
blowout fracture – can potentially break cribriform
plate, leading to dripping fluid out, which could be
snot, serum, or spinal fluid. So, its imp to know
diff’s btwn the two.
Example: wacked in the head – fluid out of ear
(otorrhea), hemorrhage leads to battle sign. This is
a fracture of the basilar plate and there is spinal
fluid there.
Most of the fluid comes out the aqueduct of sylvius
– which is the MCC of hydrocephalus in children bc
it gets blocked off until you get a build up of spinal
fluid in the 3rd vent and lateral vent, which is a
narrow area and leads to hydrocephalus. Then, it

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comes to the fourth vent and needs to get out bc it
needs to get into the subarachnoid space. So, it
goes through the foramen of Luschka and
Magendie, so fluid goes out.
Dura means strong – it’s tightly adherent to the
periosteum. So, when pt has epidural hematoma
(blood clot betwn bone and dura). The only
pressure that can split the periosteum away from
dura is arterial pressure. So, this is the one when
the middle mengial artery ruptures, and can be
done with arterial pressure (not venous).
It gets into the subarachnoid space (to protect us –
a cushion against damage). Get rid of spinal fliud
in arachonoid granulation. [A tumor can arise from
the arachnoid granulations – meningioma.] It goes
through the arachnoid granulations, (there are NO
LYMPHATICS IN BRAIN) and the dural sinuses
and conglomerate into the jugular vein, which is
emptied into the right side of the heart.
So, when you do a valsalva and the neck veins
distend, that pressure transmits all the way back to
the dural sinuses, to the arachnoid granulations
through the spinal fluid , and right down the the
needle in the subarachnoid space at L4 and the
pressure goes up. This is called quakens step
maneuver. It is a great test for when you are doing
a spinal tap to see if the entire subarachnoid space
is patent. If you don’t see that manometer go up,
there is something blocking the spinal fluid more
proximally.
Example: when you wt lift, you shouldn’t hold your
breath bc the pressure are huge and and lead to a
herniated disk.
Tentorium Cerebelli
70% of brain tumors in adults are supratentorial
(involve cerebral cortex)
70% of brain tumors in kids are infratentorial
(cerebellar, cystic astrocytoma, medulloblastoma)
Hydrocephalus
Communicating vs Noncommunicating

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Communication of spinal fluid in ventricles with
subarchnoid space.
Noncommunicating
MC
Something is preventing spinal fluid in the
ventricles from getting into the subarachnoid space
MCC = stenosed Aqueduct of Sylvius
Or something going in the 4th vent, ependymoma in
kids will block it off, or meningitis in base of brain
(TB), leads to scar tissue bc blocks foramen of
magendie and luschka.
Communicating
Still communicating, but still a build up of pressure.
One cause could be tumor of choroid plexus
(papillary looking). So, if you have a tumor there,
you have a greater ultrafiltrate of plasma and would
be making more plasma. Also, would be making
more spinal fluid. There would still be a
communication with here, but the pressure would
build up bc making more than you commonly do.
More commonly, what if you have a subarachnoid
bleed or meningitis? Then pt has scarred off
arachnoid granulations and have no way of
draining it out. So, still have a communication, but
cannot get rid of it (MC).
Arnold Chiari Malformation
Example: pull down spinal cord. This would bring
the medulla into the cervical region and maybe a lil
part of the cerebellum. Leads to hydrocephalus
and platybasia (flattening of the base of the skull)
Dandy walker syndrome
Cerebellar vermis is not developed
Herniation
Why would we herniate in the brain? Bc there is
cerebral edema and no other place to go. The
famous ones are tonsillar herniation through the
foramen magnum. (from the cerebellum) –
cerebellar herniation – has been squeezed into the
foramen magnum, and has constriction. Can
cause immediate death.

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Uncal herniation – medial portion of the temporal
lobe herniates through the tentorium cerebelli and
pressing against midbrain, leads to hemorrhage
(duret’s hemorrhage). Also an oculomotor nerve
that is gonna be compressed. So, this will lead to
opthalomoplegia (LR6SO4, 3), so everything
innervated by CN III is paralyzed. With oculomotor
nerve palsy, it is down and out. (down and in is CN
4 palsy – if CN 6 is paralyzed, will look cross eyed).
Look at pupil.
Example: MRI of oribit, name muscles
Parasympathetic constrict the pupil (normally) ,
sympathetics dilate (normally)
So, if you mess up the parasympathetics, which
normally constrict, it will lead to mydriasis.
The first sign of uncal herniation is mydriasis of
pupil on side of herniation (so it dilates on that
side). Also, posterior cerebral artery can get
blocked with uncal herniation, leading to post lobe
infarction.
Know brainstem and CN’s and how it related to
herniation
Papilledema
Any cause of increased incranial pressure
Vit A tox
Lead poisoning – delta-aminolevulinic acid – leads
to increased permeability
Audio file Day5 #6 CNS
Hydrocephalus
MCC = stenosis of the aqueduct of sylvius
Noncommunicating.
Get hydrocephalus bc the sutures have not fused
if you miss hydrocephalus in adult and sutures
have fused, will lead to dilatation of the ventricles
and eventually over years, the pressure will turn
back to normal bc the increased pressures keep
the choroid plexus from making so much
Dementia, ataxia, urinary incontinence.
Aka normal pressure hydrocephalus (bc pressures
normalize)
Tuberous Sclerosis

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AD
Hamartomas (noneoplastic proliferation of things)
Ventricles have bumps called tubercles – which are
hamartomas which have proliferation of astrocytes.
They produce hamartomas that bulge into the
ventricle, called candle stick dripping. Hemartomas
of the kidney called angiomyolipomas, MR, cardiac
tumors (rhabdomyomas), shagreen patches, areas
of hypopigmentation, woods light shine out
Anencephaly
Worst of neural tube defects
Absent brain
Vertebral arch defects
Spina bifida occulta – tufts of hair come out, vert
arches do not touch, no meninges come
Meningoceole – meninges come out
Meningomylocele – both meninges and spinal
cord come out
High alpha feto protein levels in blood of mother;
decreased in downs syndrome
Have to be on folate to prevent neural tube defects
(neural tube finished forming by 30 days, so make
sure she is on folate if she is trying to get
pregnant).
Neurofibromatosis
Albright syndrome (precocious puberty, café au lait,
bone zits)
Sturge weber
Café au lait (coffee colored non raised lesions)
spot, plexiform neurofibromas, hyperpigmentation
in the axilla (axillary freckling), neurofibromas
AD , therefore late manifestations (esp for
neurofibromatosis), penetrance, variable
expressivity (you are expressing the dz, but diff
levels of how severe the dz is)
Example: pt with HTN and pic, what test would you
get? Relationship of neurofibroma with
pheochromocytoma, therefore get a 24 hr urine for
VMA and metanephrine.
Acoustic schwannoma

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Example: pt with sensorinerual hearining loss – b9
tumor of Schwann cells around CN 8
Meningiomas
Optic nerve gliomas
Syringomyelia
Example: pt that works in factory and one of
workers says you are burning your hand and pt
didn’t notice this, on exam loss of musculature
(loss of LMN) in intrinsic muscles of the hand, loss
of pain and temp in cape like distribution across
back.
Can’t feel pain (not ALS – in ALS, first place of
development of loss of muscles is here, so don’t
confuse; but ALS is UMN and LMN loss, PURE
MOTOR , so if pt has pain, ie, this is sensory and
not ALS)
Big cystic cavity knocking off spinothalamic
knocking off pain and temp. can knock off the
corticospinal tract and anterior horn cells, so it will
be a COMBO of sensory AND motor loss for
syringiomyelia.
Infections
Meningitis vs encephalitis
Meningitis – inflammation of meninges and nuchal
rigidity; if you move your head or extend your knee,
you will stretch the meniges, leading to pain
(stretching inflamed meninges).
Encephalitis – sleeping sickness – they are always
sleeping and drowsy; they have mental status
abnormalities (not nuchal rigidity)
Pus at the base of the brain – can possibly block
lushka and majendie, leading to obstructive
hydrocephaly and noncommunicating
When you Rx meningitis, use steroids and Abs.
why? Steroids prevent scar tissue formation and
complications that arise with it (ie hydrocephalus).
This is standard TB meningitis Rx (TB in brain
causes vasculitis and scarring)
Deafness is a complication of meningitis.

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Example: pig herder, and long time problem with
focal epileptic seizures (dilating therapy) – multiple
calcified and cystic lesions in brain – dx?
Cysticercosis
Example: Jacob Cruetzfeltds from prions (mad
cow) – who is most likely to get?
Neuropathologists, neurosurgeons, beef, lettuce
from Arizona (cow manure on it)
Traumatic lesions
Epidural hematoma (above dura) – hit in head
middle meningeal – have to fracture bone (under
arterial pressures, can separate dura from
periosteum). When you get 50 mls of blood, you
get uncal herniation and die. Ie get him, say they
are ok, 6 hrs later epidural hematoma and death
Subdural hematoma – rupture of bridging veins
betwn dura and arachonoid membrane. If you
have cerebral atrophy, then the space bwtn the
dura and arachnoid membranes is bigger. Bridging
veins dangling, break and get a hematoma.
Fluctuating levels of consciousness. Left untreated
lead to dementia. Do CT to r/o epi and subdural
hematoma (also for strokes – if its a hemorrhagic
stroke)
Strokes
Slide: Brain: one side is bigger. Atherosclerotic
stroke; pale infarct of brain. At bifurcation, there is
an atherosclerotic plaque and thrombus. No blood
flow to brain and it infracted, starts breaking down,
no reperfusion, so it remains a pale infarct. If the
thrombus did break apart, and reperfusse the brain,
the blood in the goes into the area of infarction and
is called a hemorrhagic infarct. However, this
usually doesn’t occur and pale infarcts more
common. If no blood, and there is infarction, pt is a
candidate for heparin therapy. Over time, if pt
survives, ends up with cystic space where there
was infarction and this is called liquefactive
necrosis--pale infarct, liquefactive necrosis.

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Slide: hemorrhagic infarct – blood is to edge of
brain – this is an embolic infarct, usually from left
side of the heart. The vessel it always goes to is
middle cerebral artery. It gets into the Circle of
Willis and into the middle cerebral. If you embolize
down, will go into the superior mesenteric
The reason it is hemorrhagic is bc pt will get
breakdown of fibrinolytic system of the embolus
and leads to reperfusion. Instead of being a pale
infarct, it’s a hemorrhagic infarct. So, both a
atherosclerotic stroke and hemorrhagic stroke are
both infarcts – one is pale and the other is
hemorrhagic.
Slide: HTN, pressures cause lenticulostriate
vessels to come up and supply this area of the
brain. Derive from the middle cerebral aneurysms,
called Charcot Bouchard aneurysm and it ruptures,
leading to giant hematoma and blood clot. Horrible
prognosis.
So, embolic stroke goes to surface of the brain and
if it’s in the basal ganglia, it’s always an
intracebral bleed from HTN.
Example: subarachnoid hemorrhage mostly due
to rupture congenital berry aneurysm. MC at the
junction ant comm branch of ant cerebral artery
Less common cause of SAH:
AV malformation
Sturge Weber – on same side as skin lesion of the
face, there is an AV malformation
Lacunar infarcts – small areas on the brain;
unusual bc they hit areas of the brain. Depending
on where in the internal capsule, can have a pure
motor stroke or pure sensory. MC due to HTN
Multiple Sclerosis (MS)
MC demyelinating Dz (autoimmune) – MS
Slide:demylinated: white matter has myelin it, grey
doesn’t. If you are destroying white matter, then
you’ll see grey underneath. Plaques of MS.
2 ways to demylinate

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1) knock off cell that makes myelin in the brain
(oligodendrocytes in brain, schwann cell in PNS) –
viruses do this – subacute sclerosis, progressive
multifocal leukoencephalopathy, HPV – they affect
the oligodendrocyte;
2) can also have Ab’s against myelin and not the
oligodendrocyte, which is MS paresthesias
Nystagmus, ataxia, optic neuritis with blurry vision
(MCC of Optic Neuritis= MS bc demylination of
optic nerve)
Internuclear opthalmaplegia (demylination of
MLF) - pathognomonic
Spinal tap will show increased protein, normal
glucose, increase lymphs
Hydrocephalus Ex Vacuo
Severe atrophy of brain and ventricles look bigger
than they should be
Dementia
Alzheimer’s Dz
Classic lesion: senile plaque, neurit’s, amyloid
(Beta!!) – so beta amyloid is toxic and the more you
have the more toxic – pathognomonic of
alzheimers, on c’some 21, therefore seen in
down’s, neurofib tangles (in any dementia and HD)
Alz – probs in higer levels – dementia
Only way to dx is autopsy (confirmation) – see
senile plaques
Parkinson’s Dz
Resting tremor